Efficient Synthesis of Highly Functionalized Spirocarbocyclic Oxindoles through Hauser Annulation

Abstract

The synthesis of highly functionalized spirocarbocyclic oxindoles was accomplished for the first time, using a Hauser annulation strategy. A reaction between methyleneindolinones and arylsulfonylphthalides catalyzed by cesium carbonate gave access to a new class of biologically important spiro[indoline‐3,2′‐naphthalene] derivatives in very good yields.

Synthesis of Natural Products, Carbocycles, and Heterocycles by Hauser–Kraus Annulation

“…31 The Kesavan group obtained these hybrid spiro-naphthoquinone-oxindole H-K annulation products as the Boc-protected derivatives 100 through a two-step one-pot reaction. 30 These products are immediate precursors of naturally occurring spindomycins A and B.…”

Synthesis of Sulfonyloxindoles via Functional Group Exchange Between 3‐Sulfonylphthalide and Isatylidenemalononitrile

“…However, application of a vinyl nitrile as a 1,2‐dipolar synthon remained unreported. As part of our continuing interest in the synthetic applications of 3‐sulfonylphthalides towards the synthesis of novel scaffolds, [12m–p,13b–c,19] we wished to demonstrate its reactivity with isatylidenemalononitriles (Scheme 1c). We hypothesized that 3‐sulfonylphthalide 1 could take part in [4+2] annulation [Hauser‐Kraus (H−K) reaction] with isatylidenemalononitrile which will lead to spirocyclic 3‐oxindolo‐naphthoquinone.…”

Synthesis of Spiro- and Fused Heterocycles via (4+4) Annulation of Sulfonylphthalide with o-Hydroxystyrenyl Derivatives

“…Later, we also demonstrated an efficient H–K annulation of nitroalkene-derived Rauhut–Currier adducts with sulfonylphthalide to provide functionalized naphthoquinones, which in turn were transformed into functionalized phenanthrenes and azaphenanthrenes by reaction with various amine sources . Very recently, our group and the Kesavan group independently explored the H–K annulation of sulfonylphthalide and 3-olefinic oxindoles for the synthesis of biologically relevant spiro-dihydronaphthoquinoneoxindoles . Our ongoing interest toward the synthesis of complex polycyclic compounds by utilizing the 1,4-dipolar reactivity of sulfonylphthalide together with the interesting reactivity profile displayed by the Michael acceptors possessing an additional nucleophilic site, for instance, a hydroxyl group, encouraged us to evaluate the reactivity of other substrates such as o -hydroxychalcones and o -hydroxynitrostyrylisoxazoles as Michael acceptors (Scheme c).…”